Study of Bone Marrow and Blood Samples in Patients With Untreated Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia Enrolled on Clinical Trial CALGB-9621 or CALGB-9720

OBJECTIVES:

I. Determine Pgp antigen expression and Pgp-mediated functional multidrug resistance (MDR) in
pretreatment acute myeloid leukemia (AML) cells from adult patients enrolled on CALGB
clinical trials of PSC-833 Pgp modulation.

II. Correlate Pgp-mediated MDR with patient pretreatment characteristics including age,
immunophenotype, and karyotype.

III. Correlate Pgp expression, function, and in vitro modulation by PSC-833 with treatment
outcome in previously untreated AML patients treated on CALGB Pgp modulation trials.

IV. Determine Pgp expression and function in AML cells from patients with refractory or
relapsed leukemia following induction chemotherapy administered with or without PSC-833.

V. Correlate acquisition of drug resistance with changes in expression of other antigens and
gain or loss of leukemic populations at relapse in these patients.

VI. Determine the role of other mediators, including multidrug resistance-associated protein
(MRP) and lung-resistance protein (LRP), in mediating MDR in these patients at diagnosis and
with relapsed or refractory disease after induction chemotherapy with or without PSC-833.

VII. Determine the frequency of Pgp-, MRP-, and LRP- mediated MDR in adult acute
lymphoblastic leukemia cells and correlate this frequency with pretreatment characteristics
and treatment outcome in these patients.

OUTLINE:

Samples are obtained: 1) pretreatment, 2) at the time of documentation of refractory disease
in acute myeloid leukemia (AML) patients who do not achieve complete response (CR) after
induction therapy, and 3) at the time of first relapse in patients who achieve CR.

Marrow cells are preferentially used for all samples, but peripheral blood is acceptable if
marrow is not available and the blood contains 20% or more blasts. Pgp expression is measured
using flow cytometry. AML samples are analyzed by immunoenzyme techniques (IET) using
antibodies to CD33, CD34, and MRK16. B-lineage acute lymphoblastic leukemia (ALL) samples are
analyzed by IET using antibodies to CD19, CD34, and MRK16. The antibodies used to analyze
T-cells include CD7 and CD34. Pgp function is measured by growing cells in the presence of
PSC-833 in vitro and then measuring Pgp expression as above. Multidrug resistance-associated
protein (MRP) is measured using IET with the MRPm6 antibody. Lung-resistance protein (LRP) is
measured with IET and the LRP56 antibody. These results are correlated with flow cytometry
results.

Inclusion Criteria:

- Previously untreated patients eligible for and registered to a CALGB multidrug
resistance modulation treatment protocol for acute myeloid leukemia (CALGB 9621,
CALGB-9720, CALGB-19808, and CALGB 10201) OR protocols for previously untreated acute
lymphocytic leukemia

- Performance status: not specified